PROJECT SUMMARY The overall goal of this K01 application is to examine the impact of unhealthy alcohol use, cocaine use, non- prescribed opioid use, depression, and anxiety on HIV care outcomes. Despite the durability of modern antiretroviral therapy (ART) regimens, there is still a substantial minority of patients who have trouble maintaining viral suppression. Unhealthy alcohol use, other drug use, and mental health disorders have all been identified as drivers of viral non-suppression among people with HIV (PWH), yet these conditions have typically been considered independently from one another. Furthermore, the impact of these conditions is difficult to describe because symptoms are likely underreported and they are largely undertreated. Pharmacologic treatments for alcohol use disorder (AUD), opioid use disorder, depression, and anxiety are available but their long-term effects, particularly in people with comorbid substance use and mental health disorders, and particularly on HIV care continuum outcomes has been insufficiently studied. The goal of this K01 is to train the recipient to study the intersection of unhealthy alcohol use, other drug use, and mental health disorders in people with HIV, accounting for challenges in identifying these conditions. Research aims of this project are to: (1) describe the prevalence, co-occurrence, and durability of unhealthy alcohol use, cocaine use, non-prescribed opioid use, depression, and anxiety among PWH in care, accounting for underreporting of these conditions; (2) describe the care continua for AUD, opioid use disorder, cocaine use, depression, and anxiety ? that is, rates of clinical diagnoses, initiation on, and retention on pharmacologic treatment for these disorders; and (3) estimate long-term effects of pharmacologic interventions on alcohol consumption, other drug use, and mental health symptoms, and ultimately retention in HIV care and viral load. The training aims of this project are to: (1) gain understanding of current and best practices for the prevention and clinical management of unhealthy alcohol use, other drug use, and mental health disorders for PWH; (2) apply innovative methods for handling measurement error in these conditions; (3) explore Bayesian methods for one means of handling measurement error in the absence of validation data; and (4) obtain the research, writing, and administrative expertise, and preliminary data, to submit a successful R01 grant in the penultimate year of the K01 award period. Training aims will be accomplished through rigorous coursework, seminar participation, mentored and collaborative research, and conference participation. Research aims will be conducted using data from the Center for AIDS Research Network of Integrated Clinical Systems, which includes medical record data and patient reported outcomes from over 34,000 PWH engaged in clinical care from 1995-present at eight US HIV clinics. This project will address a critical gap in our understanding of how alcohol and other drug use and mental health comorbidities co-occur to impact HIV outcomes, and give clues to the potential impact that scaling up pharmacologic treatment of these comorbidities could have on ending the HIV epidemic.